Erythropoietin is a humoral regulator of erythropoiesis, which stimulates the production of erythrocytes. In normal conditions it is produced in sufficient quantities in the kidneys and the liver.
In case of hypoxic shock (such as massive blood loss), erythropoietin production needs to be increased, which means that it has to be synthesized de novo. In disease-free conditions, erythropoietin levels in circulation are extremely low.
Certain diseases or side effects of treatments of certain diseases lead to a chronic anemia that overcharges the capacity of erythropoietin production, or otherwise cannot be met by the body's own erythropoietin resources. These diseases include chronic insufficiency of the kidneys, anemias associated with malignancies, neonate anemia, chronic anemia associated with rheumatoid arthritis (ACD), anemia after bone marrow transplantation, aplastic anemia, myeloplastic syndrome and various hemoglobin-related diseases. Also anemic side effects have been shown to occur in various chemotherapies and AZT-therapy. In these cases, it may be helpful to administer EPO to increase erythrocyte production.
Human EPO is available as a recombinant protein, which ensures that sufficient quantities can be produced in a very pure form.
Several studies with recombinant human erythropoietin (r-hu-Epo) have been carried out, mainly in patients who underwent renal dialysis for chronic renal failure, in which diminished production of Epo and severe anemia requiring regular blood transfusions occur. A correction of anemia by r-hu-Epo was shown in these cases with minimal side effects.16,17,18 In AIDS patients treated with Zidovudine causing bone marrow suppression, administration of 100 U r-hu-Epo/kg thrice weekly intravenously significantly decreased transfusion requirements.19 
The invention provides a novel use of erythropoietin that is not directly related to its erythrocyte-stimulating properties. This use is specifically clear in rheumatoid arthritis, which, therefore, is more specifically described in an explanatory example for the invention.
Rheumatoid arthritis is an inflammatory disease of synovial membranes, usually expressing itself in a symmetrical polyarthritis. During the course of their disease, 70% of rheumatoid arthritis (RA) patients develop some kind of anemia,1 which may be due to iron deficiency,2,3 vitamin B12 deficiency or folic acid deficiency,4,5 hemolysis or adverse reactions to anti-rheumatic drugs.6,7 In addition, active RA is frequently (in nearly 50%) accompanied by anemia of chronic disease (ACD).8 
Factors involved in the pathogenesis of ACD are ineffective erythropoiesis,9 interleukin-1,10 tumor necrosis factor a (TNF-α),11 decreased erythropoietin synthesis5,12,13 and/or a decreased response to erythropoietin by the bone marrow.14,15 
So far, only a few studies with r-hu-Epo have been carried out in RA patients. A hemoglobin (Hb) rise was shown in two anemic RA patients treated with r-hu-Epo, 125-250 IU/kg thrice weekly, a significant hematocrit rise was recorded.20 
We have treated ten RA patients who suffered from ACD with recombinant human EPO.
In all RA patients, a rise in hemoglobin was observed. Despite a wide range of values, the increase in hemoglobin became significant after the second week of treatment with recombinant human EPO.
Besides this expected result of EPO treatment, a different unexpected benefit was obtained by the treatment.